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Xinguo JIANG


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Journal of Zhejiang University SCIENCE B 2015 Vol.16 No.1 P.44-45


Macrophage-produced IL-10 limits the chemotherapy efficacy in breast cancer

Author(s):  Xinguo Jiang

Affiliation(s):  Department of Medicine, VA Palo Alto Health Care System/Stanford University School of Medicine, Stanford, CA 94305, USA

Corresponding email(s):   xinguoj@stanford.edu

Key Words:  Breast cancer, Chemotherapy, Macrophage, IL-10, IL-12, Dendritic cell

Xinguo Jiang. Macrophage-produced IL-10 limits the chemotherapy efficacy in breast cancer[J]. Journal of Zhejiang University Science B, 2015, 16(1): 44-45.

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macrophages are among the most abundant immune cells in the tumor microenvironment, where they are known as tumor-associated macrophages (TAMs). Substantial evidence indicates that TAMs generally play protumoral roles in the primary as well as metastatic sites (Noy and Pollard, 2014). TAMs are also known to interfere with several tumor therapeutic modalities, such as chemotherapy, irradiation, and immunotherapy. In general, depletion of M2-like TAMs or reprogramming them into M1-like phenotype enhances the efficacy of these therapies (Rolny et al., 2011; de Palma and Lewis, 2013; Germano et al., 2013).


概要:本文简单介绍了最近发表在《肿瘤细胞》(Cancer Cell)上的一篇关于如何提高乳腺癌化疗疗效的文章。这篇文章发现了乳腺癌化疗可以导致促肿瘤生长的巨噬细胞数量的增多,这些巨噬细胞可以产生大量的白介素-10(IL-10),从而抑制肿瘤内树突状细胞IL-12的产生,由此抑制具细胞毒性的CD8+ T细胞的功能,最终降低化疗疗效。除此之外,文章还证明了阻断IL-10的功能可以促进乳腺癌化疗效果。这篇文章因此提出了可以降低乳腺癌化疗耐受的一种新的治疗靶点。


Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]de Palma, M., Lewis, C.E., 2013. Macrophage regulation of tumor responses to anticancer therapies. Cancer Cell, 23(3):277-286.

[2]DeNardo, D.G., Brennan, D.J., Rexhepaj, E., et al., 2011. Leukocyte complexity predicts breast cancer survival and functionally regulates response to chemotherapy. Cancer Discov., 1(1):54-67.

[3]Germano, G., Frapolli, R., Belgiovine, C., et al., 2013. Role of macrophage targeting in the antitumor activity of trabectedin. Cancer Cell, 23(2):249-262.

[4]Jiang, X., 2014. Harnessing the immune system for the treatment of breast cancer. J. Zhejiang Univ.-Sci. B (Biomed. & Biotechnol.), 15(1):1-15.

[5]Noy, R., Pollard, J.W., 2014. Tumor-associated macrophages: from mechanisms to therapy. Immunity, 41(1):49-61.

[6]Rolny, C., Mazzone, M., Tugues, S., et al., 2011. HRG inhibits tumor growth and metastasis by inducing macrophage polarization and vessel normalization through downregulation of PlGF. Cancer Cell, 19(1):31-44.

[7]Ruffell, B., Chang-Strachan, D., Chan, V., et al., 2014. Macrophage IL-10 blocks CD8+ T cell-dependent responses to chemotherapy by suppressing IL-12 expression in intratumoral dendritic cells. Cancer Cell, 26(5):623-637.

[8]Stewart, C.A., Metheny, H., Iida, N., et al., 2013. Interferon-dependent IL-10 production by Tregs limits tumor Th17 inflammation. J. Clin. Invest., 123(11):4859-4874.

[9]Trinchieri, G., 2003. Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat. Rev. Immunol., 3(2):133-146.

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